The main objective of this proposal is to better understand the metabolic consequences that result from the peripheral circulatory derangements that occur in severe congestive heart failure (CHF). To determine whether sympathetic activation is excessive during static forearm exercise and if there is a significant shift to anaerobic metabolism in the exercising forearm, forearm blood flow will be measured in the exercising limb and forearm vascular resistance (FVR) will be calculated bilaterally during static exercise. Utilizing epinephrine iontophoresis of the exercising arm and median cubital vein sampling for oxygen content, oxygen consumption and lactate production can be determined for exercising muscle in subjects and patients with significant CHF. The change in FVR of the contralateral arm and the heart rate and pressor response will serve as indices of sympathetic activation. To determine the effects of increased sympathetic tone on the metabolism of exercising muscle, the statically and dynamically contracting canine gracilis muscle will be evaluated. Muscle tension will be held constant with an analog servo mechanism and exercising blood flow, oxygen, glucose, fatty acid consumption, and lactate production determined, and glycogen, creatine phosphate and adenosine triphosphate depletion measured in serial biopsies, before and during graded norepinephrine infusion, lumbar sympathetic chain stimulation and endogenous activation of sympathetic tone. An edematous canine model of congestive heart failure will be developed and regional blood flow measured in the awake unanesthetized state, at rest and during static and dynamic exercise in the gracilis muscle. It is hoped that these studies will lead to a better understanding of the circulatory compensatory mechanisms that become operative during severe congestive heart failure and the potential deleterious effects these may have on local metabolism during exercise.